This phase I study defined the following two MTDs for clofarabine given as a 1-hour infusion daily for 5 days: 2 mg/m(2) for solid tumors, the DLT being myelosuppression; and 40 mg/m(2) for acute leukemia, the DLT being hepatotoxicity. Encouraging activity was observed in acute leukemia.

Pancreatic cancer is the fourth most common cause of adult cancer death in the U.S. The high mortality rate from pancreatic cancer is a result of the high incidence of metastatic disease at the time of diagnosis, an often fulminant clinical course, and the lack of adequate systemic therapies. Unfortunately, only 5%-25% of patients present with tumors amenable to resection. The median diseasefree survival interval following resection for operable pancreatic cancer is 13.4 months for patients treated with adjuvant gemcitabine and 6.9 months for untreated patients. A much higher percentage of patients present with metastatic disease (40%-45%) or locally advanced disease (40%), and have median survival times of 3-6 months or 8 -12 months, respectively. The frustrating lack of significant clinical advancements in the treatment of metastatic pancreatic cancer remains one of medical oncology's biggest disappointments. The past decade-long frustration has resulted in regulators, investigators, and practicing oncologists gradually lowering their standards/expectations with regard to interpreting clinical trials. Two of the more important examples of this include the approval of gemcitabine plus erlotinib and the use of a progressionfree survival advantage to defend the use of gemcitabine plus oxaliplatin. Given the marginal benefit of systemic antineoplastics, a scholarly review inclusive of other palliative strategies will help oncologists optimize the care of pancreatic cancer patients. This article examines the existing evidence in support of a role for palliative therapy in metastatic pancreatic cancer, describes recent developments with newer chemotherapeutic and molecular-targeted agents, and explores future study designs. The Oncologist 2008;13:562-576

For these reasons, efforts at identifying and treating disease-related symptomatology are priorities. This update overviews symptom management, supportive care strategies, and both standard and emerging palliative chemotherapy options. The incorporation of molecularly targeted therapies into treatment of metastatic pancreatic cancer is reviewed as well. These strategies are of relevance to internists, gastroenterologists, oncologists, and other specialists who care for patients with pancreatic cancer.

Abstract